First-line treatment for mild or moderate Clostridium difficile infection is metronidazole; vancomycin is first-line treatment for severe infection
A randomized controlled trial (RCT) showed that metronidazole was as effective as vancomycin taken orally for the treatment of mild Clostridium difficile infection. However, in cases of severe infection, 97% of patients given vancomycin had clinical resolution compared with only 76% of those given metronidazole.1 The Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America recommend metronidazole as first-line therapy for mild or moderate C. difficile infection and vancomycin for severe infection (Box 1).2 Although criteria for severe infection differ between guideline and trial, both include a leukocyte count greater than 15 × 109 cells/L.
Severity | Guidelines1 | Randomized controlled trial2 |
---|---|---|
Mild– moderate |
|
|
Severe |
| Two of:
|
Fidaxomicin is as effective as vancomycin for treatment of C. difficile infection and results in fewer relapses
In a phase 3 controlled clinical trial, fidaxomicin was noninferior to vancomycin in achieving clinical resolution of C. difficile infection.3 Of note, 13.3% of patients given fidaxomicin had recurrent infection within four weeks, compared with 24.0% of patients given vancomycin.3
Duodenal infusion of donor feces is more effective than vancomycin for recurrent infection
In an RCT comparing treatment of recurrent C. difficile infection with vancomycin or duodenal infusion of donor feces, 81% of patients in the fecal infusion group had resolution of the infection, compared with 31% of patients given vancomycin alone.4
Probiotics have no role in the treatment of C. difficile infection, and their role in prophylaxis is unclear
The latest guidelines do not recommend the use of probiotics for prophylaxis or treatment of C. difficile infection.2 A systematic review and meta-analysis of 20 RCTs found moderate-quality evidence suggesting a 34% risk reduction of C. difficile infection with the use of probiotics for prevention, with no increase in adverse events; this finding was limited by the variability of probiotic regimens and missing data in 13 studies.5 However, a recent high-quality RCT found no evidence that a multistrain probiotic preparation prevented infection.6
Phase 3 clinical trials of C. difficile vaccines are underway
The Cdiffense study is a phase 3 RCT that will evaluate the efficacy of inactivated C. difficile toxoids A and B in preventing C. difficile infection. Phase 1 trials showed development of an immune response in humans.7 Phase 2 results are forthcoming.
Footnotes
Competing interests: None declared.
This article has been peer reviewed.
For references, please see Appendix 1, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.131315/-/DC1